JP7084313B2 - アマニチンコンジュゲート - Google Patents
アマニチンコンジュゲート Download PDFInfo
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- JP7084313B2 JP7084313B2 JP2018546006A JP2018546006A JP7084313B2 JP 7084313 B2 JP7084313 B2 JP 7084313B2 JP 2018546006 A JP2018546006 A JP 2018546006A JP 2018546006 A JP2018546006 A JP 2018546006A JP 7084313 B2 JP7084313 B2 JP 7084313B2
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- 108010027164 Amanitins Proteins 0.000 title description 3
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- 231100000729 Amatoxin Toxicity 0.000 claims description 60
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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AU2017204139B2 (en) | 2016-06-17 | 2018-08-09 | Vor Biopharma, Inc. | Compositions and methods for the depletion of cells |
AU2017380099B2 (en) | 2016-12-23 | 2024-07-11 | Heidelberg Pharma Research Gmbh | Amanitin antibody conjugates |
AU2018209452B2 (en) | 2017-01-20 | 2024-11-07 | Heidelberg Pharma Research Gmbh | Compositions and methods for the depletion of CD137+ cells |
CN114191564A (zh) * | 2017-08-18 | 2022-03-18 | 四川百利药业有限责任公司 | 一种非天然鹅膏毒肽类抗体偶联物 |
KR20190043031A (ko) * | 2017-10-17 | 2019-04-25 | 한국화학연구원 | 아마톡신 유도체 및 이의 제조방법 |
WO2019090242A1 (en) * | 2017-11-04 | 2019-05-09 | Advanced Proteome Therapeutics Inc. | Composition and method for modifying polypeptides |
EP3740233A4 (en) * | 2018-01-18 | 2021-11-24 | Magenta Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR DEPLOYING CD134 + CELLS |
JP2021521202A (ja) * | 2018-04-13 | 2021-08-26 | ハイデルベルク ファルマ リサーチ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 固形腫瘍の治療のための標的化されたアマトキシン複合体 |
EP3801635A4 (en) * | 2018-06-07 | 2022-04-06 | Magenta Therapeutics, Inc. | THERAPEUTIC METHODS USING ANTIBODY-DRUG CONJUGATE (ADC) |
CA3107383A1 (en) | 2018-07-23 | 2020-01-30 | Magenta Therapeutics, Inc. | Use of anti-cd5 antibody drug conjugate (adc) in allogeneic cell therapy |
CN112739339A (zh) * | 2018-07-23 | 2021-04-30 | 美真达治疗公司 | 抗cd137抗体药物缀合物(adc)在同种异体细胞疗法中的用途 |
WO2020127968A1 (en) | 2018-12-20 | 2020-06-25 | Marino Stephen F | Protein-drug conjugate comprising a monomeric form of proteinase 3 |
CA3125751A1 (en) * | 2019-01-07 | 2020-07-16 | Magenta Therapeutics, Inc. | Use of an anti-cd45 antibody drug conjugate (adc) in cell therapy |
EP3958908A1 (en) * | 2019-04-24 | 2022-03-02 | Heidelberg Pharma Research GmbH | Amatoxin antibody-drug conjugates and uses thereof |
BR112021023226A2 (pt) | 2019-05-23 | 2022-01-04 | Heidelberg Pharma Res Gmbh | Composto, conjugado, método para sintetizar os conjugados e composição farmacêutica |
EP3792250A1 (en) * | 2019-09-13 | 2021-03-17 | Pure Bioorganics SIA | Synthesis of alpha-amanitin and its derivatives |
US20220298204A1 (en) * | 2019-07-05 | 2022-09-22 | Pure Bioorganics Sia | Synthesis of a-amanitin and its derivatives |
AR120218A1 (es) * | 2019-10-15 | 2022-02-02 | Heidelberg Pharma Res Gmbh | Conjugados de amatoxina y anticuerpo específico de linfocitos b |
EP4161946A1 (en) * | 2020-06-09 | 2023-04-12 | Heidelberg Pharma Research GmbH | Method for synthesis of thioether-containing peptides |
CA3195572A1 (en) | 2020-11-04 | 2022-05-12 | Heidelberg Pharma Research Gmbh | Composition comprising a combination of immune checkpoint inhibitor and antibody-amatoxin conjugate for use in cancer therapy |
CN116615219A (zh) * | 2020-12-22 | 2023-08-18 | 中外制药株式会社 | 包括利用混合溶剂的冷冻干燥工序的药品的制造方法 |
AR125130A1 (es) | 2021-03-19 | 2023-06-14 | Heidelberg Pharma Res Gmbh | Conjugados de amatoxina y anticuerpo específicos de linfocitos b |
US20240165257A1 (en) | 2022-11-01 | 2024-05-23 | Heidelberg Pharma Research Gmbh | Anti-gucy2c antibody and uses thereof |
WO2024121632A1 (en) | 2022-12-09 | 2024-06-13 | Crispr Therapeutics Ag | Use of anti-cd117 antibody drug conjugate (adc) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015519906A (ja) | 2012-06-04 | 2015-07-16 | アイアールエム・リミテッド・ライアビリティ・カンパニーIrm,Llc | 部位特異的標識法およびそれによって生成される分子 |
JP2015533490A (ja) | 2012-09-12 | 2015-11-26 | ジェンザイム・コーポレーション | 変更されたグリコシル化および低減されたエフェクター機能を有するFc含有ポリペプチド |
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---|---|---|---|---|
DK0463151T3 (da) | 1990-01-12 | 1996-07-01 | Cell Genesys Inc | Frembringelse af xenogene antistoffer |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
US6613879B1 (en) | 1999-05-14 | 2003-09-02 | Boehringer Ingelheim Pharma Kg | FAP-activated anti-tumour compounds |
ATE521366T1 (de) | 2006-05-27 | 2011-09-15 | Faulstich Heinz Dr | Anwendung von amatoxin-konjugaten und phallotoxin-konjugaten mit makromolekülen zur krebstherapie und therapie von entzündungen |
TW200942243A (en) | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
CL2009000505A1 (es) | 2008-03-05 | 2010-01-15 | Biocryst Pharm Inc | Compuestos derivados de triciclos nitrogenados, inhibodores de polimerasas de adn y arn virales; composicion farmaceutica que los comprende; y uso en el tratamiento de infecciones virales y cancer. |
KR20110140124A (ko) | 2009-04-08 | 2011-12-30 | 하인즈 파울스티히 | 암치료용 아미톡신-활성 표적 결합 부위 |
SI3192529T1 (sl) | 2009-04-08 | 2020-07-31 | Faulstich, Heinz Dr. | Z amatoksinom ojačane vezne komponente terapevtske celične površine, zasnovane za zdravljenje tumorjev |
AU2010283632B2 (en) | 2009-08-10 | 2016-08-25 | Ucl Business Plc | Reversible covalent linkage of functional molecules |
CN102933236B (zh) | 2010-04-15 | 2014-10-08 | 斯皮罗根有限公司 | 吡咯并苯二氮卓类及其结合物 |
ES2402254T3 (es) * | 2010-09-30 | 2013-04-30 | Heidelberg Pharma Ag | Conjugados de amatoxinas con ligadores mejorados |
EP2497499A1 (en) | 2011-03-10 | 2012-09-12 | Heidelberg Pharma GmbH | Amatoxin-conjugates with improved linkages |
EP2684865A1 (en) | 2012-07-13 | 2014-01-15 | Heidelberg Pharma GmbH | Methods for synthesizing amatoxin building block and amatoxins |
MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
US20150218220A1 (en) * | 2012-09-12 | 2015-08-06 | Brian Alan MENDELSOHN | Amatoxin derivatives and cell-permeable conjugates thereof as inhibitors of rna polymerase |
CN105377304B (zh) * | 2014-03-10 | 2018-05-15 | 海德堡医药有限责任公司 | 鹅膏毒肽衍生物 |
BR112017019300B1 (pt) * | 2015-03-09 | 2023-02-23 | Heidelberg Pharma Gmbh | Conjugado de fórmula genérica (ama l x s)n ab, método para sintetizar um conjugado de fórmula genérica (ama l x s)n ab, kit, composição farmacêutica e uso da composição farmacêutica |
US11166912B2 (en) | 2016-03-03 | 2021-11-09 | Ctt Pharma Inc. | Orally administrable composition |
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JP2015533490A (ja) | 2012-09-12 | 2015-11-26 | ジェンザイム・コーポレーション | 変更されたグリコシル化および低減されたエフェクター機能を有するFc含有ポリペプチド |
Non-Patent Citations (1)
Title |
---|
LIANG ZHAO et al.,SYNTHESIS OF A CYTOTOXIC AMANITIN FOR BIORTHOGONAL CONJUGATION,CHEMBIOCHEM,ドイツ,2015年06月03日,Vol.16,pp.1420-1425,http://dx.doi.org/10.1002/cbic.201500226 |
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